Effectiveness of Screening and Decolonization of S. aureus in Surgery Outpatients Staphylococcus aureus (SA) healthcare-associated infections (HAI) cause significant morbidity and mortality. SA causes 15% of all HAI and 30% of surgical site infections (SSIs). Each year over 40 million Americans undergo operations, 1-10% of whom will acquire SSIs. Such infections double the length of hospitalization and risk of dying, and increase U.S. health care costs by $5-10 billion/year. We need effective interventions to prevent SSIs caused by either methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) strains. Nasal carriers of SA (25-30% of adults) have a 2-14 times greater risk than non-carriers of acquiring an SA SSI. A potential prevention approach is routine pre-operative screening of patients, followed by decolonization of identified SA carriers. The long term goal of this research is to reduce the incidence of SSIs caused by SA, both MSSA and MRSA strains. This will help improve the safety and effectiveness of health care for Americans. Achievement of this goal requires that we first address the following critical knowledge gaps: (i) which surgical patients should be screened pre-operatively; (ii) which body site(s) should be screened for optimal SA detection, and (iii) which decolonization approach is optimal for outpatient use. The immediate goal, and the focus of this R03 proposal, is to conduct the research needed to determine pre-operative SA carriage rates (including by strain type and site of carriage), to evaluate the practicality (adherence, cost) of a SA decolonization protocol that is self-administered by patients at home. propose to conduct a randomized clinical trial (RCT) of the efficacy of nasal mupirocin ointment, CHG mouth rinse, and CHG pre-operative bathing, as performed by the patient at home for 5 days pre-operatively. This protocol will be compared with the current standard of care, usually 1-2 showers with an antiseptic soap before the procedure. Briefly, the aims are as follows: Aim 1: Determine the efficacy of a novel decolonization protocol, compared with standard of care, for eradicating SA carriage pre-operatively in surgery out-patients. We hypothesize that the SA eradication rate will be 2-3 times higher in the intervention arm compared with the standard of care arm. Aim 2: Obtain data to inform sample size calculations and cost estimates for a RCT to prevent SSIs, determine screening requirements, and assess treatment adherence. We will: determine the proportion of pre-operative patients who are SA carriers and the sites of carriage, by SA type, MSSA, CA-MRSA, and HA- MRSA, determine adherence to the study intervention and standard of care, reasons for non-compliance, and gather cost data to provide preliminary evidence of potential cost-effectiveness of the intervention. Aim 3: Identify risk factors (demographic, medical) for SA carriage (overall and separately for MSSA and MRSA, split by CA- and HA-MRSA). Gather preliminary data on SSIs in study subjects.